Deliberate self-poisoning in Australian adolescents is increased on school days.

Deliberate self-poisoning (DSP) in adolescents is increasing dramatically. Life at school is one of the most important life influences for this age group. This study aimed to investigate whether the frequency of DSP is higher during school term compared to holidays and whether this difference has become greater over time. This is an ecological study using Poisons Information Centre (PIC) data for all DSPs in 10-19 year olds from New South Wales, Tasmania and Australian Capital Territory that occurred between 2005 and 2018. For each call, the date of the poisoning was assigned as 'term' or 'holiday'. To control for population growth, calls were expressed as per 100,000 of the population per day. Multivariable Poisson regression was performed to investigate the combined impact of various predictors (state, sex, year, holiday/term, day of week, age) on call number. 26,432 calls were included in the analysis (73.6% female, 24.1% male and 2.3% unknown). Poisson regression showed significant effects for all predictors, with an increased likelihood of DSP during the school term compared with holidays and on Monday-Thursday compared with Saturday but only during the school term. DSP doubled between 2012 and 2017 and the disparity between DSP that occurs during term vs. holiday increased over that time frame. We conclude that some of the increase in DSP is likely due to school-specific stressors, hence the school environment is the ideal setting for self-harm prevention initiatives.

Acute alcohol use in Australian coronial suicide cases, 2010-2015.

BACKGROUND: Acute use of alcohol is a robust risk factor for suicide, reported in approximately one- to two-fifths of suicide cases. Comparisons of risk factors between suicides with and without prior acute alcohol consumption have not been investigated in Australia. This study addresses the gap by examining individual factors (age, sex, employment status, method of suicide) and environmental factors (month of death, jurisdiction) between alcohol and non-alcohol suicide. METHODS: Data for all suicide deaths (aged 15 and over) in Australia were obtained from the National Coronial Information System (NCIS). Blood alcohol concentrations (BAC) were extracted from coronial reports, along with demographic information. Alcohol consumption prior to suicide was assumed if BAC ≥ 0.05 g/100 mL. We compared case characteristics between alcohol related and non-alcohol related suicides using logistic regression. RESULTS: 26.7% of suicide deaths in Australia had a BAC ≥ 0.05 g/100 mL. Alcohol use prior to suicide was associated with male gender (adjusted odds ratio [AOR]: 1.14, 95% confidence interval [95%CI]: 1.03, 1.26), being aged between 35-44 years (AOR: 1.26, 95%CI: 1.08, 1.46) and hangings (AOR: 1.53, 95%CI: 1.08, 1.46). Mean suicides per month over the timeframe demonstrated significant seasonality. Mean counts per month for alcohol related suicides peaked in December, compared to a peak in September for non-alcohol related suicides. CONCLUSIONS: This study highlights differences between alcohol related and non-alcohol related suicides including sex, age, method of death, time of year and location within Australia. Targeting alcohol related suicide should be a key priority in comprehensive suicide prevention strategies.

Effect of age on the severity of chronic lithium poisoning.

Objectives: Severe lithium toxicity is commonly observed in older people. We aimed to determine the extent to which age is associated with increased severity of chronic lithium poisoning and of which a range of possible factors might explain the associations.Method: We did a retrospective review of patients aged ≥15 years old with serum lithium concentrations ≥1.3 mmol/L from three hospitals. Clinical details, treatment and outcomes were recorded. eGFR, creatinine and lithium clearance were calculated. The severity of lithium toxicity was graded into five categories (Amdisen score). ANOVA was used to quantify the association between age and severity. Spearman correlation coefficient was used to explore relationships between age and different factors expected to alter severity. Ordinal regression analysis was used to determine the interdependence of age and these factors and age on severity of lithium toxicity.Results: From 2008-2018, there were 242 patients with a median age of 56.5 years (IQR: 41-69). There were 156 females (64%). There was a statistically significant association between Amdisen severity scores and age (p = .0004). The median calculated eGFR was 65 mL/min/1.73 m2 (IQR: 41-91) with a corresponding estimated lithium clearance of 18 mL/min (IQR: 13.8-22.8). There was no correlation of age with initial serum lithium concentration (p = .76). There was a strong correlation between age and estimated lithium clearance (r = -0.72, 95% CI: -0.78 to -0.66, p < .001), lithium daily dose (r = -0.65, 95% CI: -0.72 to -0.57, p < .0001) and lithium concentration/dose (r = 0.62, 95% CI: 0.53-0.69, p < .0001). There was a weak correlation between age and infection (r = 0.18, 95% CI: 0.04-0.31, p = .009) and drug interactions (r = 0.25, 95% CI: 0.11-0.37, p = .0003). Ordinal regression indicated the independent predictors for severity of lithium toxicity were lithium concentration (p < .0001) and lithium clearance (p = .03) adjusted for age and dose.Conclusions: Despite lower lithium doses, older patients had more severe toxicity. Increased severity of lithium toxicity in the elderly is largely explainable by decreased lithium clearance from multiple factors such as age-related decline in renal function, drug interactions and infection.

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming.

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. SUMMARY: Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient.

Monitoring treatment of acute kidney injury with damage biomarkers.

BACKGROUND: Damage biomarkers may identify mechanisms and sites of acute kidney injury (AKI). However, the utility of novel AKI biomarkers differs by context, and their utility for monitoring treatment of AKI is unknown. We hypothesized that selected AKI biomarkers would facilitate monitoring of mechanism-specific treatment. We examined this using a panel of biomarkers to monitor cisplatin-induced AKI treatment with alpha-lipoic acid (α-LA) that has previously been demonstrated to ameliorate cisplatin induced AKI. METHODS: AKI was induced in male Sprague Dawley rats using cisplatin (6mg/kg) in the presence or absence of a single dose of α-LA (100mg/kg). A panel of 12 urinary kidney damage biomarkers (CystatinC, NGAL albumin, alpha-1-acid glycoprotein, clusterin, KIM-1, osteopontin, total protein, cytochrome C, epidermal growth factor, interleukin-18 and malondialdehyde was examined as well as histological injury, serum creatinine and cystatin C, and clinical parameters. RESULTS: Cisplatin treatment modified all parameters, except interleukin-18 and malondialdehyde, with each parameter demonstrating a different temporal profile. α-LA treatment attenuated renal tubular injury scores (P <0.05), decreased peak serum creatinine (p=0.004) and cystatin C (p=0.04), and urinary damage biomarkers of proximal tubular injury (CystatinC, NGAL, albumin, and alpha-1-acid glycoprotein). Other urinary biomarkers were not modified. Neither α-LA alone, nor the cisplatin vehicle (DMSO) modified biomarker profiles. CONCLUSIONS: α-LA treatment ameliorated cisplatin-induced AKI. Protection was demonstrated by reduced structural damage, improved glomerular filtration and reduced excretion of urinary biomarkers of proximal tubular damage. Effective treatment of AKI can be monitored by site and perhaps by mechanism-specific kidney damage biomarkers.

Digoxin-specific antibody fragments in the treatment of digoxin toxicity.

CONTEXT: Digoxin-specific antibody fragments (digoxin-Fab) are widely regarded as a safe and effective treatment for the management of acute and chronic digoxin poisoning. Calculated equimolar doses of digoxin-Fab are high, very expensive, and infrequently used. OBJECTIVE: To review the pharmacology, efficacy, effectiveness, indications, safety and the dosage of digoxin-specific antibody fragments. METHODS: Pubmed, Embase, Medline and Cochrane were searched from 1946 to May 2013 using the terms digoxin, digoxin-specific Fab, and digoxin antibody. Pharmacology and kinetics of digoxin and digoxin-Fab. Digoxin acts via inhibition of Na⁺/K⁺ ATPase. It has a narrow therapeutic index. Digoxin has 60-80% bioavailability, a mean plasma half-life of 40 h and a volume of distribution (Vd) of 5-10 L/kg and low protein binding (20%). A 40-mg vial of digoxin-Fab (DigiFab) binds 0.5 mg digoxin. Digoxin-Fab has a mean plasma half-life of 19-30 h and a Vd of 0.4 L/kg. The half-lives of both digoxin and digoxin-Fab are prolonged in renal failure to over 100 h. Efficacy and effectiveness of digoxin-Fab. There were no randomised clinical trials examining the use of digoxin-Fab for acute or chronic digoxin poisonings. Ten case series with a total of 2,080 patients have reported on the use of digoxin-Fab in digoxin poisoning. In three large case series of 430 acute and 1308 chronic poisonings, response rates to digoxin-Fab vary from 80-90% to 50%. The time for reversal of digoxin toxicity is reported to be 30-45 min. Studies with pharmacokinetic data showed that free digoxin concentration fell to almost zero within a few minutes following the administration of digoxin-Fab. Digoxin-Fab was used more frequently in acute than chronic digoxin poisoning with a higher reported success rate when used in acute overdose. It is sometimes recommended to use full neutralisation doses (based on serum concentration × Vd or ingested dose). It has also been proposed to use half this dose. Indications for digoxin-Fab. Patients who have life-threatening tachy-bradyarrhythmias, hyperkalaemia (> 6 mmol/L) or haemodynamic instability with an elevated digoxin concentration (> 2 µg/L or 2.6 nmol/L). The lowest effective digoxin-Fab dosing regimen has not been established. Safety of digoxin-Fab. Adverse events such as exacerbation of heart failure, increased ventricular rate and hypokalaemia are uncommon (< 10%). Recrudescence of digoxin toxicity and allergic reactions are infrequent. Digoxin-Fab dosing in acute poisoning. Digoxin load based on ingested dose will generally overestimate digoxin-Fab doses as bioavailability is 60-80%, and further reduced by vomiting and activated charcoal. Digoxin load based on concentration also will be overestimated when the concentration is taken before distribution is complete (around 6 h). Much smaller doses of digoxin-Fab can eliminate the digoxin in the central compartment (Vd ≈ 55 L). In imminent cardiac arrest, it may be justified to give a full neutralising dose. Otherwise, based on pharmacokinetic modelling, it is recommended to give 80 mg bolus digoxin-Fab, repeated as required according to clinical parameters because the onset of clinical response is usually rapid. Most patients would be expected to require a total of less than half of the calculated neutralising dose using this strategy. Digoxin-Fab dosing in chronic poisoning. Even if digoxin load is estimated following distribution (> 6 h), excessive neutralisation doses may still be calculated because of variation in Vd due to equations failing to account for lean body weight, age and renal failure. In practice, it is suggested to give 40 mg (1 vial) digoxin-Fab at a time and repeat after 60 min if patient is still symptomatic, sooner if patient is clinically unstable. In general, 40-120 mg (1-3 vials) should be sufficient. CONCLUSIONS: Digoxin-Fab is safe and indicated in all patients with life-threatening arrhythmias and an elevated digoxin concentration. However, calculated full neutralising doses of digoxin-Fab are expensive and may not be required. In acute poisoning, a small bolus of 80 mg, repeat if necessary, titrated against clinical effect, is likely to achieve equivalent benefits with much lower total doses. With chronic poisoning, it may be simplest to give 40 mg (1 vial) digoxin-Fab at a time and repeat after 60 min if there is no response.

Diagnostic 20-min whole blood clotting test in Russell's viper envenoming delays antivenom administration.

BACKGROUND: The 20-min whole blood clotting test (WBCT20) is widely used for the identification of coagulopathy in snake envenoming, but its performance in practice has not been evaluated. AIM: We aimed to investigate the diagnostic utility of the WBCT20 for coagulopathy in Russell's viper envenoming. DESIGN: Prospective observational study. METHODS: Adult patients with snake envenoming were recruited. Age, sex, bite information, clinical effects, serial WBCT20 and antivenom treatment were recorded. Definite Russell's viper envenoming was confirmed with venom specific enzyme immunoassay. We assessed sensitivity of admission WBCT20 to coagulopathy (international normalized ratio, INR > 1.5) in Russell's viper envenoming, the specificity of negative WBCT20 in non-envenomed patients and directly compared paired WBCT20 and INR. RESULTS: Admission WBCT20 was done in 140 Russell's viper bites with coagulopathy and was positive in 56/140 [sensitivity 40% (95% confidence interval (CI): 32-49%)]. A negative WBCT20 led to delayed antivenom administration [WBCT20-ve tests: median delay, 1.78 h (interquartile range (IQR): 0.83-3.7 h) vs. WBCT20 + ve tests: median delay, 0.82 h (IQR: 0.58-1.48 h); P = 0.0007]. Delays to antivenom were largely a consequence of further WBCT20 being performed and more common if the first test was negative (41/84 vs. 12/56). Initial WBCT20 was negative in 9 non-envenomed patients and 48 non-venomous snakebites [specificity: 100% (95% CI: 94-100%)]. In 221 paired tests with INR > 1.5, the WBCT20 was positive in 91(41%). The proportion of positive WBCT20 only increased slightly with higher INR. CONCLUSION: In clinical practice, the WBCT20 has low sensitivity for detecting coagulopathy in snake envenoming and should not over-ride clinical assessment-based decisions about antivenom administration. There is an urgent need to develop a simple bedside test for coagulopathy in snake envenoming.

A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18).

BACKGROUND: Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming. OBJECTIVES: To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation. PATIENTS/METHODS: This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs. no FFP within 4 h of antivenom administration. Patients (> 2 years) recruited to the Australian snakebite project with VICC (International Normalized Ratio [INR] > 3) were eligible. Patients were randomized 2 : 1 to receive FFP or no FFP. The primary outcome was the proportion with an INR of < 2 at 6 h after antivenom administration. Secondary outcomes included time from antivenom administration to discharge, adverse effects, major hemorrhage, and death. RESULTS: Of 70 eligible patients, 65 consented to be randomized: 41 to FFP, and 24 to no FFP. Six hours after antivenom administration, more patients randomized to FFP had an INR of < 2 (30/41 [73%] vs. 6/24 [25%]; absolute difference, 48%; 95% confidence interval 23-73%; P = 0.0002). The median time from antivenom administration to discharge was similar (34 h, range 14-230 h vs. 39 h, range 14-321 h; P = 0.44). Seven patients developed systemic hypersensitivity reactions after antivenom administration - two mild and one severe (FFP arm), and three mild and one severe (no FFP). One serious adverse event (intracranial hemorrhage and death) occurred in an FFP patient with pre-existing hypertension, who was hypertensive on admission, and developed a headache 6 h after FFP administration. Post hoc analysis showed that the median time from bite to FFP administration was significantly shorter for non-responders to FFP than for responders (4.7 h, interquartile range [IQR] 4.2-6.7 h vs. 7.3 h, IQR 6.1-8 h; P = 0.002). CONCLUSIONS: FFP administration after antivenom administration results in more rapid restoration of clotting function in most patients, but no decrease in discharge time. Early FFP administration (< 6-8 h) post-bite is less likely to be effective.

Validity of referral hospitals for the toxicovigilance of acute poisoning in Sri Lanka.

OBJECTIVE: To identify the hospital admission data set that best captures the incidence of acute poisoning in rural Sri Lanka. METHODS: Data were collected on all acute poisoning cases admitted to 34 primary and 1 referral hospital in Anuradhapura district from September 2008 to January 2010. Three admission data sets were compared with the "true" incidence of acute poisoning to determine the systematic bias inherent to each data set. "True" incidence was calculated by adding all direct admissions (not transfers) to primary hospitals and to the referral hospital. The three data sets were: (i) all admissions to primary hospitals only; (ii) all admissions to the referral hospital only (direct and referrals), and (iii) all admissions to both primary hospitals and the referral hospital ("all admissions"). The third is the government's routine statistical method but counts transfers twice, so for the study transferred patients were counted only once through data linkage. FINDINGS: Of 3813 patients admitted for poisoning, 3111 first presented to a primary hospital and 2287 (73.5%) were later transferred to the referral hospital, where most deaths (161/177) occurred. All data sets were representative demographically and in poisoning type, but referral hospital data yielded a more accurate case-fatality rate than primary hospital data or "all admissions" data. Admissions to primary hospitals only or to the referral hospital only underestimated the incidence of acute poisoning by about 20%, and data on "all admissions" overestimated it by 60%. CONCLUSION: Admission data from referral hospitals are easily obtainable and accurately reflect the true poisoning incidence.

Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos.

BACKGROUND: Many organophosphorus (OP) insecticides have either two O-methyl or two O-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures. AIM: We aimed to describe the clinical course and responsiveness to therapy of people poisoned with two S-alkyl OP insecticides-profenofos and prothiofos. DESIGN: We set up a prospective cohort of patients with acute profenofos or prothiofos self-poisoning admitted to acute medical wards in two Sri Lankan district hospitals. Clinical observation was carried out throughout their inpatient stay; blood samples were taken in a subgroup for assay of cholinesterases and insecticide. RESULTS: Ninety-five patients poisoned with profenofos and 12 with prothiofos were recruited over 5 years. Median time to admission was 4 (IQR 3-7) h. Eleven patients poisoned with profenofos died (11/95; 11.6%, 95% CI 5.9-20); one prothiofos patient died (1/12; 8.3%, 95% CI 0.2-38). Thirteen patients poisoned with profenofos required intubation for respiratory failure (13/95; 13.7%, 95% CI 7.5-22); two prothiofos-poisoned patients required intubation. Both intubations and death occurred late compared with other OP insecticides. Prolonged ventilation was needed in those who survived-a median of 310 (IQR 154-349) h. Unexpectedly, red cell AChE activity on admission did not correlate with clinical severity-all patients had severe AChE inhibition (about 1% of normal) but most had only mild cholinergic features, were conscious, and did not require ventilatory support. CONCLUSION: Compared with other commonly used OP insecticides, profenofos and prothiofos are of moderately severe toxicity, causing relatively delayed respiratory failure and death. There was no apparent response to oxime therapy. The lack of correlation between red cell AChE activity and clinical features suggests that this parameter may not always be a useful marker of synaptic AChE activity and severity after OP pesticide poisoning.

Potential for methotrexate exposure through contamination during parenteral use as an immunosuppressant.

BACKGROUND: To evaluate whether the risk of methotrexate (MTX) exposure through skin contamination using parenteral doses of 25 mg warrants special oncology handling precautions during administration. METHODS: We conducted a study with six human volunteers deliberately exposed to an entire dose of 25 mg MTX solution on their skin for 30 min. Serum levels of MTX were measured at baseline, 2, 4, 8, 12 and 24 h as well as serum homocysteine at baseline and 24 h after clinical exposure. Twenty-four-hour urinary excretion of MTX and possible local or systemic signs of toxicity were also recorded. RESULTS: All MTX serum concentrations were less than 0.02 micromol/L within the 24-h period. This is 500 times below the recommended serum concentration for which folinic acid supplementation is recommended. There was also no significant increase in homocysteine level to suggest MTX toxicity. The only adverse effects were mild local dermal reactions in three female volunteers. CONCLUSION: Deliberate skin contamination and possible inhalation of a 25 mg MTX solution failed to show significant or quantifiable serum and urine concentrations to suggest MTX toxicity. Precautions to prevent contact with MTX designed for oncology protocols are unnecessary for our rheumatology patients or their carers using these much lower immunosuppressant doses for autoimmune diseases.

Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration.

BACKGROUND: Paraquat is a herbicide with a good occupational safety record, but a high mortality after intentional ingestion that has proved refractory to treatment. For nearly three decades paraquat concentration-time data have been used to predict the outcome following ingestion. However, none of the published methods has been independently or prospectively validated. We aimed to use prospectively collected data to test the published predictive methods and to determine if any is superior. METHODS: Plasma paraquat concentrations were measured on admission for 451 patients in 10 hospitals in Sri Lanka as part of large prospective cohort study. All deaths in hospital were recorded; patients surviving to hospital discharge were followed up after 3 months to detect delayed deaths. Five prediction methods that are based on paraquat concentration-time data were then evaluated in all eligible patients. RESULTS: All methods showed comparable performance within their range of application. For example, between 4- and 24-h prediction of prognosis was most variable between Sawada and Proudfoot methods but these differences were relatively small [specificity 0.96 (95% CI: 0.90-0.99) vs. 0.89 (0.82-0.95); sensitivity 0.57 vs. 0.79, positive and negative likelihood ratios 14.8 vs. 7.40 and 0.44 vs. 0.23 and positive predictive values 0.96 vs. 0.92, respectively]. CONCLUSION: All five published methods were better at predicting death than survival. These predictions may also serve as tools to identify patients who need treatment and for some assessment to be made of new treatments that are trialled without a control group.

Survival after massive hydroxychloroquine overdose.

Hydroxychloroquine overdose is infrequently reported and the majority of recommendations come from the greater experience with chloroquine poisoning. We report two cases of massive hydroxychloroquine poisoning (20 g in each case), both of which received advanced cardiac life support and a treatment regimen consisting of sodium bicarbonate, adrenaline and potassium. Both these patients survived beyond their initial rapid deterioration and cardiovascular collapse to be discharged from hospital without sequelae. These patients had the highest reported non-lethal serum concentrations (13.8 and 26.0 mg/l). They both demonstrated rapid recovery from a pre-arrest condition, following aggressive correction of electrolyte and pH disturbance and rapid distribution of the drug to peripheral tissues.

Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity.

OBJECTIVE: In severe paracetamol hepatotoxicity, orthotopic liver transplant (OLT) is a standard treatment in patients judged to have a hopeless prognosis. The most commonly used criteria to make this decision are the King's College Criteria (KCC). We aimed to compare the expected survival for patients who meet the KCC and do not receive transplant and those who receive OLT. METHODS: A systematic review of studies of survival in patients who met the KCC according to whether they were transplanted. Data from these studies was extrapolated to compare long-term survival with and without adjustment for Quality of Life. RESULTS: The survival of patients meeting KCC and undergoing transplant has not been specifically studied. UK data on transplants for acute liver failure indicate 1 and 10 year survival rates of 65 and 44%, respectively. Survival in those without transplant was documented in 15 studies. The average long-term survival rate was 24.9%. Survival was worse in studies originating in the King's unit (13.8 vs. 30.0%). It was apparent that this may be due to spectrum bias occurring in this much larger unit. There was clear evidence that those with the best prognosis were preferentially transplanted at the Kings liver unit, indicating the criteria may perform significantly worse at predicting death without transplant than previously estimated. Even so, for a 20-year-old meeting KCC, the best estimate of life expectancy with transplant (13.5 years) is no better than without (13.4 years). Adjustment for quality of life made OLT clearly a worse option. CONCLUSION: Criteria for OLT that have a much higher positive predictive value (for death without transplant) are required. Such studies must be conducted only on those who would be considered suitable for transplant. Non-orthotopic liver transplant may be a preferred option in such circumstances, although much more data on survival after this procedure are required.

Predicting outcome using butyrylcholinesterase activity in organophosphorus pesticide self-poisoning.

BACKGROUND: The usefulness of a low butyrylcholinesterase (BuChE) activity on admission for predicting severity in acute organophosphorus (OP) insecticide poisoning has long been debated. Previous studies have been confounded by the inclusion of multiple insecticides with differing inhibitory kinetics. AIM: We aimed to assess the usefulness of admission BuChE activity, together with plasma OP concentration, for predicting death with two specific organophosphorus insecticides. DESIGN: A prospective cohort of self-poisoned patients. METHODS: We prospectively studied 91 and 208 patients with proven dimethoate or chlorpyrifos self-poisoning treated using a standard protocol. Plasma butyrylcholinesterase activity and OP concentration were measured on admission and clinical outcomes recorded. RESULTS: The usefulness of a plasma BuChE activity <600 mU/ml on admission varied markedly--while highly sensitive in chlorpyrifos poisoning (sensitivity 11/11 deaths; 100%, 95% CI 71.5-100), its specificity was only 17.7% (12.6-23.7). In contrast, while poorly sensitive for deaths in dimethoate poisoning [12/25 patients; 48%, (27.9-68.7)] it was reasonably specific [86.4% (75.7-93.6)]. A high OP concentration on admission was associated with worse outcome; however, a clear threshold concentration was only present for dimethoate poisoning. CONCLUSION: Plasma BuChE activity on admission can provide useful information; however, it must be interpreted carefully. It can only be used to predict death when the insecticide ingested is known and its sensitivity and specificity for that insecticide has been studied. Plasma concentration of some OP insecticides predicts outcome. The development of rapid bedside tests for OP detection may aid early assessment of severity.

Predicting outcome in acute organophosphorus poisoning with a poison severity score or the Glasgow coma scale.

BACKGROUND: Organophosphorus (OP) pesticide poisoning kills around 200,000 people each year, principally due to self-poisoning in the Asia-Pacific region. AIM: We wished to assess whether patients at high risk of death could be identified accurately using clinical parameters soon after hospital admission. DESIGN: We evaluated the usefulness of the International Program on Chemical Safety Poison Severity Score (IPCS PSS) and the Glasgow Coma Score (GCS) prospectively for predicting death in patients poisoned by OP pesticides. METHODS: Data were collected as part of a multicenter cohort study in Sri Lanka. Study doctors saw all patients on admission, collecting data on pulse, blood pressure, pupil size, need for intubation and GCS. RESULTS: Of the patients, 1365 with a history of acute OP poisoning were included. Receiver operating characteristic (ROC) curves were calculated for the IPCS PSS and GCS on admission. The IPCS PSS and GCS had similar ROC area under the curves (AUC) and best cut points as determined by Youden's index (AUC/sensitivity/specificity 0.81/0.78/0.79 for IPCS PSS > or = grade 2 and 0.84/0.79/0.79 for GCS < or = 13). The predictive value varied with the pesticide ingested, being more accurate for dimethoate poisoning and less accurate for fenthion poisoning (GCS AUC 0.91 compared with 0.69). CONCLUSION: GCS and the IPCS PSS were similarly effective at predicting outcome. Patients presenting with a GCS < or = 13 need intensive monitoring and treatment. However, the identity of the organophosphate must be taken into account, since the half of all patients who died from fenthion poisoning only had mild symptoms at presentation.

Urinary alkalinisation for acute chlorophenoxy herbicide poisoning.

BACKGROUND: Acute poisoning with chlorophenoxy herbicides (such as 2,4-D, MCPA, 2,4,5-T and mecoprop) is reported worldwide, potentially causing severe toxicity and death in exposed patients. Animal studies support the application of urinary alkalinisation (particularly using sodium bicarbonate) in the management of acute chlorophenoxy herbicide poisoning to facilitate excretion of these herbicides. Some case reports of human exposure have suggested benefit from urinary alkalinisation also. OBJECTIVES: To assess the efficacy of urinary alkalinisation, in particular sodium bicarbonate, for the treatment of acute chlorophenoxy herbicide poisoning. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CENTRAL, Current Awareness in Clinical Toxicology, Info Trac, http://www.google.com.au, and Science Citation Index of studies identified by the previous searches. The bibliographies of identified articles were reviewed and experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials of urinary alkalinisation in patients ingesting a chlorophenoxy herbicide and presenting within 24 to 48 hours of poisoning were sought. The quality of studies and eligibility for inclusion was assessed using criteria by Jadad and Schulz. DATA COLLECTION AND ANALYSIS: Authors independently extracted data from the identified studies using a pre-designed form. Study design, including the method of randomisation, participant characteristics, type of intervention and outcomes were all recorded. MAIN RESULTS: No studies were identified which satisfied inclusion criteria. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of urinary alkalinisation for acute chlorophenoxy herbicide poisoning. A well conducted randomised controlled trial is urgently required to determine whether the efficacy and indications of this treatment.

Identification of strategies to prevent death after pesticide self-poisoning using a Haddon matrix.

Despite pesticide self-poisoning causing around 300 000 deaths each year in the rural Asia Pacific region, no comprehensive public health response has yet been formulated. The authors have developed a Haddon matrix to identify factors that increase the risk of fatal rather than non-fatal pesticide self-poisoning in Sri Lanka. Many important host factors such as age, gender, and genetics are not alterable; factors that could be changed-alcohol use and mental health-have previously proved difficult to change. Interventions affecting agent or environmental factors may be easier to implement and more effective, in particular those limiting the human toxicity and accessibility of the pesticides, and the quality, affordability, and accessibility of health care in the community. Controlled studies are required to identify effective strategies for prevention and harm minimization and to garner political support for making the changes necessary to reduce this waste of life. Lessons learnt from Sri Lanka are likely to be highly relevant for much of rural Asia.